RESUMO
Coumarins have great pharmacotherapeutic potential, presenting several biological and pharmaceutical applications, like antibiotic, fungicidal, anti-inflammatory, anticancer, anti-HIV, and healing activities, among others. These molecules are practically insoluble in water, and for biological applications, it became necessary to complex them with cyclodextrins (CDs), which influence their bioavailability in the target organism. In this work, we studied two coumarins, and it was possible to conclude that there were structural differences between 4,7-dimethyl-2H-chromen-2-one (DMC) and 7-methoxy-4-methyl-2H-chromen-2-one (MMC)/ß-CD that were solubilized in ethanol, frozen, and lyophilized (FL) and the mechanical mixtures (MM). In addition, the inclusion complex formation improved the solubility of DMC and MMC in an aqueous medium. According to the data, the inclusion complexes were formed and are more stable at a molar ratio of 2:1 coumarin/ß-CD, and hydrogen bonds along with π-π stacking interactions are responsible for the better stability, especially for (MMC)2@ß-CD. In vivo wound healing studies in mice showed faster re-epithelialization and the best deposition of collagen with the (DMC)2@ß-CD (FL) and (MMC)2@ß-CD (FL) inclusion complexes, demonstrating clearly that they have potential in wound repair. Therefore, (DMC)2@ß-CD (FL) deserves great attention because it presented excellent results, reducing the granulation tissue and mast cell density and improving collagen remodeling. Finally, the protein binding studies suggested that the anti-inflammatory activities might exert their biological function through the inhibition of MEK, providing the possibility of development of new MEK inhibitors.
Assuntos
Cumarínicos , Cicatrização , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Cumarínicos/química , Cumarínicos/farmacologia , Animais , Cicatrização/efeitos dos fármacos , Camundongos , Humanos , Solubilidade , MasculinoRESUMO
Autism Spectrum Disorder (ASD) is a disorder with different etiologies and poor elucidation, characterized by changes in social and cognitive skills. ASD impacts a large number of people in the world. Surprisingly, in spite of its great importance, just modest progress has been achieved towards comprehending this pathology and designing new therapies. The molecular dysfunctions observed in people with autism are evidenced by the interference in the synthesis of synaptic proteins, which impairs their development and plasticity, leading to characteristics of individuals with ASD. The present work investigates the mTOR pathway and the proteins related to its regulation and neurological functioning. The path of protein synthesis and translation is promising to treat various disorders and its elucidation may, for example, result in drugs that facilitate the diagnosis and broaden the range of treatments, improving the quality of life of ASD patients.